Geometrical and thermodynamic stability of govaniadine scaffold adducts with dopamine receptor D1

Abstract

Govaniadine, an isoquinoline alkaloid first isolated from Corydalis govaniana Wall., has been reported to possess multiple biological properties. Its potential as a possible dopamine receptor D1 modulator has been assessed in this research work along with its 3D similar structures for hit molecule optimization by in silico methods. Server-based molecular docking calculations were performed to find the best docked pose of the top molecules in terms of binding affinity and total energy. The molecular level details of the ligand molecules interacting with the amino acid residues near the orthosteric site of the dopamine receptor D1 (PDB ID: 7X2F) were elaborated. The stability of the protein-ligand adduct as determined from 200 ns molecular dynamics simulation in terms of structural parameters like root mean square deviation, root mean square fluctuation, radius of gyration, solvent accessible surface area, and hydrogen bond count was reasonable and free energy change from −35.46 ± 2.91 kcal/mol to −16.87 ± 2.91 kcal/mol from molecular mechanics generalized Born surface area method hinted at the spontaneity of the forward reaction for the top molecules. Ligand 626 (PubChem CID: 71109986) could be chosen as a hit candidate with better geometrical and thermodynamic stability and could be a possible modulator. The preliminary results point towards the need for further characterization of govaniadine scaffold-derived hit molecules for their development as effective and safe drug candidates by various experimental and computational techniques.

Keywords

• Free energy
• MMGBSA
• Molecular docking
• Molecular dynamics
• Natural product
• Phytochemical